Evaluation of the effect of ketamine on remifentanil-induced hyperalgesia: a double-blind, randomized study ★

• Remifentanil has been associated with postoperative hyperalgesia.
• Ketamine reduced remifentanil-induced hyperalgesia at a site distant from the surgery.
• Ketamine did not reduce remifentanil-induced hyperalgesia at the incision site.
• Ketamine did not reduce inflammatory response in individuals using remifentanil.

Abstract study objectiveOpioids are associated with hyperalgesia that can reduce their analgesic effect. The aim of this study was to determine whether the addition of ketamine reduces remifentanil-induced hyperalgesia; improves its analgesic effect; and alters interleukin 6 (IL-6), IL-8, and IL-10 levels.DesignThis is a prospective, randomized, double-blind study.SettingThe setting is in a operating room and ward in a university hospital.PatientsThere are 56 patients, aged ≥ 18 years, American Society of Anesthesiologists I or II, who underwent laparoscopic cholecystectomy.InterventionsAnesthesia was induced with remifentanil, 50% oxygen, and isoflurane. Patients randomized to group 1 received remifentanil (0.4 μg/kg per minute) and ketamine (5 μg/kg per minute), and patients randomized to group 2 received remifentanil (0.4 μg/kg per minute) and saline solution. Postoperative analgesia was achieved using morphine via patient-controlled analgesia.MeasurementsThe measurements were postoperative pain intensity during 24 hours; morphine consumption; time to first morphine supplementation; hyperalgesia (using monofilaments and an algometer) and allodynia (using a soft brush) in the thenar eminence of the nondominant hand and in the periumbilical region 24 hours after surgery; extent of hyperalgesia using a 300-g monofilament near the periumbilical region 24 hours after surgery; and serum levels of IL-6, IL-8, and IL-10.Main resultsGroups were similar for baseline characteristics. There were no differences in pain intensity, time to first request of morphine, and total 24 hours dose of morphine between groups. There was a difference in hyperalgesia using monofilaments 24 hours after the surgery in the thenar eminence of the nondominant hand, with a better profile for the experimental group. However, there were no differences in hyperalgesia using an algometer, in allodynia using a soft brush; in extent of hyperalgesia; or in levels of IL-6, IL-8, and IL-10.ConclusionsIt was not possible to demonstrate that the addition of ketamine (5 μg/kg per minute) is effective in preventing or reducing remifentanil-induced postoperative hyperalgesia in laparoscopic cholecystectomy.